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| United States Patent |
5,118,354
|
|
Ammeraal
, et al.
|
*
June 2, 1992
|
Method for making branched cyclodextrins and product produced thereby
Abstract
Branched cyclodextrins are made from crystalline cyclodextrin in a
fluidized state in an acid environment at a temperature between
110.degree. C. and 170.degree. C.
| Inventors:
|
Ammeraal; Robert (11661 S. Nagle Ave., Worth, IL 60482);
Benko; Larry (335 Persimmon Dr., Schererville, IN 46375);
Kozlowski; Ronald (4156 Sheffield Ave., Hammond, IN 46327)
|
| [*] Notice: |
The portion of the term of this patent subsequent to February 14, 2006
has been disclaimed. |
| Appl. No.:
|
609899 |
| Filed:
|
November 6, 1990 |
| Current U.S. Class: |
127/40; 127/38; 127/46.1; 127/63; 514/58; 536/103 |
| Intern'l Class: |
C08B 030/18; C13F 003/00; C13F 005/00 |
| Field of Search: |
127/40,38,63,46.1
536/103
514/58
|
References Cited
U.S. Patent Documents
| 4303787 | Dec., 1981 | Horikoshi et al.
| |
| 4668626 | May., 1987 | Kobayashi et al.
| |
| 4781977 | Nov., 1988 | Yagi et al.
| |
| 4808232 | Feb., 1989 | Beesley.
| |
| 4840679 | Jun., 1989 | Ammeraal et al.
| |
| 4871840 | Oct., 1989 | Kobayashi et al.
| |
| 4904307 | Feb., 1990 | Ammeraal et al. | 127/40.
|
| 4910137 | Mar., 1990 | Kobayashi et al.
| |
Other References
Kennedy et al., "Starch and Dextrin" in Whistler et al., Starch Chemistry
and Technology, Academic Press NY (1984) pp. 596-599.
Morton "Pyrolysis if Starch" in Whistler et al., Starch Chemistry and
Technology, Academic Press NY, vol. I pp. 421-437 (1964).
|
Primary Examiner: Morris; Theodore
Assistant Examiner: Brunsman; David M.
Parent Case Text
This is a continuation-in-part of U.S. patent application Ser. No. 467,804
filed Jan. 19, 1990 now U.S. Pat. No. 5,032,182 which in turn is a
divisional of U.S. patent application Ser. No. 232,389 filed Aug. 15,
1988, now U.S. Pat. No. 4,904,307 issued Feb. 27, 1990.
Claims
What is claimed is:
1. A process for making branched cyclodextrin comprising:
(a) heating crystalline cyclodextrin to a temperature between about
110.degree. C. to about 170.degree. C. in the presence of an acid catalyst
and water while maintaining the cyclodextrin, catalyst and water in a
fluidized state to form a product containing branched cyclodextrin; and
(b) separating branched cyclodextrin from the product.
2. The process of claim 1 wherein the crystalline cyclodextrin is beta
cyclodextrin and the branched cyclodextrin is branched beta cyclodextrin.
3. The process of claim 1 wherein the acid catalyst is a mineral acid.
4. The process of claim 1 wherein the acid catalyst is hydrogen chloride
gas.
5. The process of claim 1 wherein the pH of the cyclodextrin after addition
of the acid catalyst is about 1.0 to about 6.0.
6. A process for making branched cyclodextrin comprising the steps of:
(a) fluidizing a crystalline cyclodextrin in an acid environment while
heating the fluidized cyclodextrin to a temperature between about
110.degree. C. to 170.degree. C. for about 1 to about 3 hours to produce
branched cyclodextrin; and
(b) recovering the branched cyclodextrin.
7. The process of claim 6 wherein the cyclodextrin is beta cyclodextrin.
Description
This invention relates to a method for producing branched cyclodextrins and
especially branched beta cyclodextrins and the product produced thereby.
Starch occurs naturally in a variety of plants such as corn, potato,
sorghum and rice and is extracted from portions of the plant by a milling
operation which separates the starch from the plant. Physically, the
starch is in a granular form which typically comprises both amylose and
amylopectin.
Amylose is a Linear polymer of anhydroglucose units bonded together by
alpha 1,4 glycosidic bonds while amylopectin is a polymer composed of a
straight chain of alpha 1,4 anhydroglucose units onto which side chains of
alpha 1,4 anhydroglucose polymers are bonded. In amylopectin, the bond
between the straight chain and the side chain is an alpha 1,6 glycosidic
bond. The amount of amylose and amylopectin in a starch granule depends on
the source of the starch. For example, starch obtained from high amylose
corn contains about a 50:50 ratio while starch obtained from waxy corn
contains about a 99:1 ratio of amylopectin to amylose.
Cyclodextrins, also called Schardinger dextrins, cycloamyloses,
cyclomaltoses and cycloglucans, are polymers of anhydroglucose bonded
together by alpha 1,4 bonds to form a ringed compound. A six membered ring
is called alpha cyclodextrin; seven, beta cyclodextrin; and eight, gamma
cyclodextrin. These six, seven and eight membered rings are also referred
to as cyclomaltohexaose, cyclomaltoheptaose and cyclomaltooctaose,
respectively.
Branched cyclodextrins were described as early as 1965 by French and his
co-workers, but had been studied very little until recently. Branched
cyclodextrins, as their name implies, have one or more anhydroglucose
units bonded onto the ring structure such that a branch extends out from
the ring structure.
Conventionally, branched cyclodextrins are obtained by treating a starch
slurry high in amylopectin, such as waxy starch, with an enzyme or acid to
produce a gelatinized and liquefied starch slurry having a DE between 1
and 5. The gelatinized and liquefied starch slurry is then treated with
cyclodextrin glycosyl transferase (CGT), at the appropriate pH,
temperature and time for the selected CGT. The enzyme, CGT, is obtained
from microorganisms such as Bacillus macerans, B. magaterium, B.
circulans, B. stearothermophilus and Bacillus sp. (alkalophilic) as well
as others. The digest from the gelatinized and liquefied starch slurry
treated with CGT contains branched cyclodextrins, non-branched
cyclodextrins, and acyclic material. This digest typically has a low
concentration of branched cyclodextrins. The branched cyclodextrins and
cyclodextrins are then typically separated from the digest by a solvent
extraction process.
In order to produce predominately beta cyclodextrins and branched beta
cyclodextrins, the reaction between CGT and the gelatinized and liquefied
starch slurry is conducted under a solvent such as toluene or p-xylene.
Such solvents substantially increase the yield of both beta cyclodextrin
and branched beta cyclodextrin.
Another method for forming branched cyclodextrins is taught in U.S. Pat.
No. 4,668,626 issued May 26, 1987. The '626 patent teaches another
enzymatic method for producing branched cyclodextrins.
In both enzymatic treatments to obtain branched cyclodextrins, it is though
that the bond between the branch and the cyclodextrin ring is an alpha 1,6
glycosidic bond, the same bond as between the branches and the main chain
in amylopectin.
Then, in 1990, U.S. Pat. No. 4,904,307 issued on Feb. 27, 1990. The '307
patent teaches heating dry crystalline cyclodextrin to a temperature
between about 135.degree. C. to about 220.degree. C. for a period of time
sufficient to produce branched cyclodextrin. Preferably, the cyclodextrins
used in the process of the '307 patent are dry as defined therein. It is
stated in the '307 patent that the use of dilute mineral acids can be
employed in the conversion; however, it is stated that this is not
preferred. It is also stated in the '307 patent that the preferred
temperature range is about 180.degree. C. to about 190.degree. C.
An improved process for making branched cyclodextrins in a pyrolysis
process has now been discovered. It has now been discovered that by
converting cyclodextrin to branched cyclodextrin at a lower temperature
range than the preferred temperature range of the '307 patent in the
presence of an acid catalyst and water while maintaining the reaction
components in a fluidized state that superior results to those obtained in
the '307 patent are possible. These superior results include better color
and higher yields. It was also found that the rate of conversion of
cyclodextrin to branched cyclodextrin is faster in the process of the
present invention compared to the process of the '307 patented process.
It has also been found that the process of the present invention readily
scales up and, specifically, the process of the present invention has been
scaled up to produce forty five (45) kilogram batches. As will be
appreciated by those of skill in the art, such scale up is important for a
commercial application.
Broadly, the process of the present invention comprises fluidizing
crystalline cyclodextrin in the presence of an acid catalyst and water at
a temperature between about 110.degree. C. to about 170.degree. C. to form
a product containing branched cyclodextrins. The branched cyclodextrins
are then separated from the product.
The cyclodextrins used in the process of the present invention are from any
source of starch and produced by any process. Cyclodextrins are made in a
conventional manner. Good results have been obtained using cyclodextrins
produced from corn starch.
Conventionally, cyclodextrins are made by forming an aqueous solution of
starch at a concentration up to about 35% by weight solid. The slurry is
then subjected to gelatinization and liquefaction by enzyme or acid to a
DE from about 1 to about 5. The preferred enzyme for liquefaction is
bacterial alpha amylase. Next, a selected CGT is added to the gelatinized
and liquefied slurry and the pH, temperature and time of the treatment are
adjusted depending on the selected CGT. Generally, the pH is between about
4.5 to about 8.5, and the temperature ranges from ambient to about
75.degree. C. The time of reaction runs for about ten hours to seven days.
Cyclodextrins are then separated from solution by precipitation in a
conventional manner. Commericial sources of cyclodextrins are available.
Alpha, beta and gamma cyclodextrins are used in the present invention
either as a mixture or individually. Preferably, only one type of
cyclodextrin is used in the process and the types are not mixed. Good
results have been obtained with beta cyclodextrin.
The cyclodextrins must be in the crystalline form and washed free of
non-carbohydrate impurities. If the cyclodextrins are not in the
crystalline form, they must be crystallized. Crystallization is
accomplished in a conventional manner by forming a solution of
cyclodextrins and cooling the solution and holding it in a cooled state
for about two days. Crystals form from the cooled solution. Then the
crystals are washed in a conventional manner to remove the
non-carbohydrate impurities.
The process of the present invention must be conducted in the presence of
water. Specifically, the cyclodextrin should have a moisture level greater
than about 5% and preferably between about 5% and about 20%. More
preferred, the cyclodextrin used in the present invention has a moisture
content of about 11% to about 15%. Good results have been obtained when
the cyclodextrin used in the process of the present invention had a
moisture content of about 12%. Moisture content is measured in a
conventional manner.
It has been found that the cyclodextrin used in the process of the present
invention, although starting with a moisture content as stated above,
dries out during the conversion. Once the water has been eliminated, the
conversion by means of acid stops. If additional conversion is desired,
the temperature must be raised to above about 170.degree. C.; however,
conversion at such a high temperature has been found to result in
formation of a colored product. Alternatively, to continue the conversion
of cyclodextrins to branched cyclodextrins in the presence of acid,
additional moisture is added to maintain the moisture content of the
cyclodextrin, during reaction, to within the above stated ranges. This
need for moisture in the process of the present invention has been found
to be in direct contradiction to the process of the '307 patent which is
conducted on dry cyclodextrin. Specifically, it has been found that in the
absence of acid, as taught by the process of the '307 patent, that during
the conversion of the cyclodextrins to branched cyclodextrins the moisture
level drops to below about 3.0% before conversion of the cyclodextrins to
branched cyclodextrins starts to occur.
The fact that conversion ceases when moisture is no longer present in the
process of the present invention gives an advantage over the process of
'307 where overconversion and melting can occur. In other words, the
process is self-limiting.
The crystallized cyclodextrin, no matter whether it is alpha, beta, or
gamma, should be substantially free of non-carbohydrate materials and
acyclic carbohydrate materials. Good results have been obtained with
crystalline cyclodextrins having a purity of above about 95% by weight.
Preferably, the size of the crystals should be such that the crystals pass
through a 100 mesh screen; however, they should not be so small as to
cause a dusting problem.
The conversion should be conducted at a temperature between about
110.degree. C. to about 170.degree. C. A more preferred temperature is
about 120.degree. C. to about 140.degree. C. and good results have been
obtained at a temperature of about 130.degree. C.
Time for such a reaction depends on the moisture level, pH of cyclodextrins
and temperature. Typically, about one to about three hours are needed. At
about 130.degree. C. and a moisture level of about 12%, it has been found
that the water disappears after about one to about two hours and that the
conversion ceases. The process is generally conducted at ambient pressure.
The conversion is carried out in the presence of an acid catalyst, such as
dilute mineral acid, calcium chloride, aluminum chloride, phosphorous
acid, chlorine and monochloracetic acid. Preferably a dilute mineral acid
such as hydrochloric, sulfuric or nitric acid is used. The preferred
mineral acid is hydrochloric acid and good results have been obtained
using hydrogen chloride gas. The amount of acid catalyst used is
sufficient to adjust the pH to between about 1.0 and about 6.0 and more
preferably between about 1.5 and about 5.0. Good results have been
obtained with a pH of about 3.0.
In order to maintain the cyclodextrins in a fluidized state during
conversion, conventional equipment is employed. Good results have been
obtained with a dextrin cooker sold under the name Littleford which is a
horizontally oriented cooker with a paddle arrangement and air purge that
maintains the cyclodextrins in a fluidized state. The cooker is operated
in a standard manner.
After the conversion, the product is removed from the reactor and allowed
to cool to ambient temperature.
Finally, the branched cyclodextrins must be separated from the other
components of the process. Any conventional method of separation is
employed.
A practical method for separating the branched cyclodextrins from the
non-branched cyclodextrins is described in U.S. Pat. No. 4,840,679 issued
Jun. 20, 1989, incorporated herein by reference.
Broadly, the '679 patent teaches a separation process for separating
branched beta cyclodextrins from acyclic and beta cyclodextrins
comprising: forming a first precipitate and a first liquor from a first
aqueous solution containing branched beta cyclodextrin by the addition of
a beta cyclodextrin complexant to the first solution; recovering the first
precipitate; forming a second aqueous solution with the first precipitate;
forming a second solution by the addition of a beta cyclodextrin
complexant to the second solution; recovering the second liquor; and
finally, recovering branched beta cyclodextrins from the second liquor.
Preferably, the branched cyclodextrins are separated from the non-branched
cyclodextrins as taught in U.S. patent application Ser. No. 232,307 filed
Aug. 15, 1988, now U.S. Pat. No. 5,007,967 incorporated herein by
reference. This application teaches separating branched cyclodextrins from
non-branched cyclodextrins by passing the mixtures through a matrix onto
which an inclusion compound has been bound. The branched cyclodextrins and
cyclodextrins are sequentially eluted from the column.
Once the branched cyclodextrins are separated from the other components of
the product, the unreacted cyclodextrins are preferably reused in the
conversion step.
These and other aspects of the present invention may be more fully
understood by reference to the following examples.
EXAMPLE 1
This example illustrates making a branched beta cyclodextrin without an
acid catalyst and without fluidization.
Crystalline beta cyclodextrin crystals, in an amount of 46.5 lbs. (10.2%
moisture), were placed in a 35 liter jacketed heating vessel equipped with
an agitator. The agitator had a shaft with two 45.degree. angle blades on
the shaft. The vessel was operated at 200.degree. C. and the beta
cyclodextrin crystals were maintained at 190.degree. C. for 3.2 hours.
After the 31/4 hour period, the contents of the pot were removed and
branched beta cyclodextrin separated. Table I below lists the results:
TABLE I
______________________________________
% formed of branched 7.8
beta cyclodextrin
% Beta cyclodextrin 22.8
degraded during heating
% degraded beta cyclodextrin
34.2
converted to branched
beta cyclodextrin
% unreacted beta cyclodextrin
77.2
% purified branched 5.3
cyclodextrin recovered
Color*
Hunter Whiteness -8.4
Hunter Blue 55.9
______________________________________
*The test for color used a reflectance spectrophotometer manufactured by
Hunter Labs.
The purified branched cyclodextrin product from this conversion was
visually yellow in color. The product was subjected to a conventional
carbon bleach treatment and ion exchange treatment in an attempt to obtain
a colorless product. However, such treatment did not result in a colorless
product.
EXAMPLE 2
This example illustrates making a branched cyclodextrin wherein the
conversion takes place with an acid catalyst in the presence of water. The
cyclodextrins during conversion are maintained in a fluidized state.
Into a cooker made by Littleford Company 45.2 Kg. (99.5 lbs., 12% moisture)
of crystalline beta cyclodextrin was placed. The cooker was closed and
hydrogen chloride gas was added to lower the pH to 3.1. The cooker mixer
shaft was rotated at 150 rpm with an air purge so as to maintain the
acidified cyclodextrin in a fluidized state. The cooker had a steam heated
jacket in which 150 psi steam was injected allowing for a maximum
temperature of 175.degree. C. The temperature of the contents of the
cooker, after acid addition, rose from 64.degree. C. to 167.degree. C.
during the conversion. The contents of the cooker were sampled at 1.0,
1.5, 2.0 and 2.2 hours. The results of the sampling are listed in Table II
below:
TABLE II
______________________________________
1.0 hr.
1.5 hr. 2.0 hr. Final (2.2 hr.)
______________________________________
Temperature (.degree.C.)
125 137 162 167
Moisture (%) 9% 2.4% 1.0% 1.0%
Reducing sugars (DE)*
0.0 3.9 2.1 1.8
Hunter Whiteness
93.7 89.3 13.8 9.3
Hunter Blue -- 97.3 -- --
% Acyclic 1.0 24.8 46.1 49.3
% Branched beta
2.4 22.0 29.8 27.4
cyclodextrin
% Beta cyclodextrin
96.6 53.2 24.1 23.3
% Purified branched
-- 20.9 -- --
cyclodextrin recovered
______________________________________
*Lane-Eynon
By comparing the results in Table II at 1.5 hours to the results in Table
I, it can be seen that the color of branched beta cyclodextrin made in
accordance with the present invention is whiter than branched beta
cyclodextrin made by another process. It can be seen that the amount of
branched beta cyclodextrin made in Example 2 is about three times that
made in Example 1. It is also readily apparent that both time and
temperature in Example 2 are less than in Example 1.
EXAMPLE 3
Using the cooker of Example 2 above, 45.4 Kg (100 lbs., 12% moisture) of
beta cyclodextrin were acidified with hydrogen chloride gas to a pH of
3.0. Samples were taken throughout the conversion and the results are
listed in Table III below:
TABLE III
______________________________________
Sample 1 2 3 4 5 6 7
______________________________________
Time (hr.)
0 0.5 .75 1.0 1.125 1.75 2.0
Temperature
113 112 127 129 130 130 129
(.degree.C.)
Moisture (%)
7.6 2.8 -- 0.2 -- -- --
Reducing .32 1.40 3.50 3.40 5.14 2.52 2.33
Sugars (DE).sup.1
Relative 1.0 1.6 3.3 6.6 9.5 12.7 13.4
Color.sup.2
% Acyclic
0 9.8 24.2 34.5 36.1 37.4 37.6
% Branched
0 8.6 19.1 23.7 22.9 23.0 22.0
beta CD
% Beta 100 81.6 56.7 41.8 41.0 39.6 40.3
cyclodextrin
______________________________________
1 LaneEynon
2 Pacific Scientific Y value Color at time `0` was 0.64 and was set at
1.0
As will be evident to one of skill in the art, the method to produce
branched cyclodextrins is similar in some respects to the production of
dextrins from starch by pyrolysis.
It will be understood that the preferred embodiments of the present
invention herein chosen for the purpose of illustration are intended to
cover all changes and modifications of the preferred embodiments of the
present invention which do not constitute a departure from the spirit and
scope of the invention.
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